Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000990527
Ethics application status
Approved
Date submitted
15/07/2024
Date registered
13/08/2024
Date last updated
13/08/2024
Date data sharing statement initially provided
13/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study Assessing the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of K-3505 in Healthy Volunteers (PART I).
Scientific title
A Study Assessing the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of K-3505 in Healthy Volunteers (PART I).
Secondary ID [1] 312377 0
K-3505 P001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Migraine 334168 0
Condition category
Condition code
Neurological 330836 330836 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
K-3505 P001 (PART I) is a study of K-3505 in healthy male and female participants. This will be the first administration of K-3505 to humans.

This is a single rising dose study composed of 2 sequential panels of 8 subjects each (Panels A and B), each having Screening (up to 28 days prior to first dose of study drug), Treatment, and Follow-Up (approximately 14 days after their last dose of study medication) periods. The Treatment period will include up to 4 dosing periods per panel.

All periods for both panels will involve a single administration of K-3505 or placebo except for the final dosing period for Panel B. In the final panel tested, anticipated to be Panel B, Period 4, subjects will receive the same dose of K-3505 (or placebo) on 2 consecutive days. The dose of K-3505 used in this period will be within a range that was well tolerated during the dose escalation. Dosing is double blind meaning that neither the study participants nor the unit staff will know whether a participant is receiving K-3505 or placebo in a given treatment period.

Subjects will participate in either Panel A or Panel B and be randomized to a treatment sequence within that panel. This will result in subjects being assigned to K-3505 or placebo in a 3:1 ratio in each dosing period. All subjects will be randomized to receive placebo in 1 of the 4 dosing periods. For each panel, there will be at least 4 days between each dosing period.
Planned doses of K-3505 are noted below. All doses of K-3505 and placebo will be administered by intravenous (i.v.) infusion over approximately 2 minutes. All doses of K-3505 and placebo will be admiistered by nursing staff.

Panel A
• Period 1: 3 micrograms K-3505 or placebo
• Period 2: 10 micrograms K-3505 or placebo
• Period 3: 30 micrograms K-3505 or placebo
• Period 4: 90 micrograms K-3505 or placebo
Panel B
• Period 1: 250 micrograms K-3505 or placebo
• Period 2: 750 micrograms K-3505 or placebo
• Period 3: 2000 micrograms K-3505 or placebo
• Period 4: Dosing of K-3505 or placebo on 2 consecutive days. The dose of K-3505 will be the same on both days and will be within the range of doses that was well tolerated in earlier periods.

In all dosing periods, subjects will be admitted into the study unit on the day prior to K-3505 or placebo administration (Day -1). They will fast a minimum of 8 hours (overnight fast) prior to K-3505 or placebo administration and will remain domiciled for at least 24 hours after K-3505 or placebo administration for safety monitoring and to assess pupillary responses. In the two-day dosing period (planned for Panel B Period 4), subjects will also fast overnight from Day 1 to Day 2 and will be discharged after the completion of the Day 2 24-h assessments.
Intervention code [1] 328926 0
Treatment: Drugs
Comparator / control treatment
Placebo will be sterile 0.9% normal saline administered i.v.

Control group
Placebo

Outcomes
Primary outcome [1] 338664 0
To assess the safety and tolerability of single rising i.v. doses of K-3505.
Timepoint [1] 338664 0
TEAs are AEs that start or worsen during or after the first dose of study medication.

For Panel A, TEAEs will be assessed in Period 1 on Day 1 (after dosing) and Day 2, in Periods 2-4 on Day -1, Day 1 and Day 2, and at the post-study visit 14 days after the final dose.

For Panel B, TEAEs will be assessed in Period 1 on Day 1 (after dosing) and Day 2, in Periods 2 and 3 on Day -1, Day 1 and Day 2, in Period 4 on Day -1, and Days 1, 2, and 3, and at the post-study visit 14 days after the final dose.

For any subjects from Panel A or B who discontinue study medication early, TEAEs will also be assessed at the early termination (ET) visit.

Discontinuation of study medication for a TEAE may occur between start of dosing in Period 1 and completion of dosing in Period 4.






Secondary outcome [1] 436935 0
To characterize the plasma pharmacokinetics (PK) of K-3505.
Timepoint [1] 436935 0
PK timepoints include -
Panel A and Panel B/All Periods : Day 1: Predose, End of Infusion (EOI), 10, 20, 30, 60, 120, 180 minutes postdose
Panel B Period 4: Day 2: Predose, EOI, 10, 20, 30, 60, 120, 180 minutes postdose
Secondary outcome [2] 436936 0
To characterize the plasma PK of K-3505.
Timepoint [2] 436936 0
PK timepoints include -
Panel A and Panel B/All Periods : Day 1: Predose, End of Infusion (EOI), 10, 20, 30, 60, 120, 180 minutes postdose
Panel B Period 4: Day 2: Predose, EOI, 10, 20, 30, 60, 120, 180 minutes postdose
Secondary outcome [3] 436939 0
To characterize the plasma PK of K-3505.
Timepoint [3] 436939 0
PK timepoints include -
Panel A and Panel B/All Periods : Day 1: End of Infusion (EOI)
Panel B Period 4: Day 2: EOI
Secondary outcome [4] 436940 0
To characterize the plasma PK of K-3505.
Timepoint [4] 436940 0
PK timepoints include -
Panel A and Panel B/All Periods : Day 1: Predose, End of Infusion (EOI), 10, 20, 30, 60, 120, 180 minutes postdose
Panel B Period 4: Day 2: Predose, EOI, 10, 20, 30, 60, 120, 180 minutes postdose
Secondary outcome [5] 437376 0
To characterize the plasma PK of K-3505.
Timepoint [5] 437376 0
PK timepoints include -
Panel A and Panel B/All Periods : Day 1: Predose, End of Infusion (EOI), 10, 20, 30, 60, 120, 180 minutes postdose
Panel B Period 4: Day 2: Predose, EOI, 10, 20, 30, 60, 120, 180 minutes postdose
Secondary outcome [6] 437377 0
To characterize the plasma PK of K-3505.
Timepoint [6] 437377 0
PK timepoints include -
Panel A and Panel B/All Periods : Day 1: Predose, End of Infusion (EOI), 10, 20, 30, 60, 120, 180 minutes postdose
Panel B Period 4: Day 2: Predose, EOI, 10, 20, 30, 60, 120, 180 minutes postdose
Secondary outcome [7] 437378 0
To characterize the plasma PK of K-3505.
Timepoint [7] 437378 0
PK timepoints include -
Panel A and Panel B/All Periods : Day 1: Predose, End of Infusion (EOI), 10, 20, 30, 60, 120, 180 minutes postdose
Panel B Period 4: Day 2 Predose, EOI, 10, 20, 30, 60, 120, 180 minutes postdose

Eligibility
Key inclusion criteria
1.Must have given written informed consent
2. Be willing and able to comply with the study schedule of visits, all trial procedures and restrictions, including following study diet requirements.
3. Be between 18 to 45 years of age, inclusive, at the time of signing informed consent.
4. Have a body mass index (BMI) of 18.5 to 30.0. kg/m2, inclusive.
5. Be a non smoker/non-user of tobacco or other nicotine products, who has not used tobacco- or nicotine-containing products (eg, nicotine patch) for at least 1 month before administration of the initial dose of trial drug, has used no more than 5 tobacco or nicotine forms (eg less than or equal to 5 cigarettes) per week within 3 months of screening, and agrees to abstain from smoking tobacco or the use of nicotine-containing products throughout study participation (through completion of the Poststudy visit).
6. Be judged to be in good health by the Investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead ECG, and vital sign measurements performed at the Screening Visit and before administration of the initial dose of trial drug.
7. Dark-adapted pupil diameter (measured with pupillometer after greater than or equal to 5 minutes at approximate 5 lux) is between 5.0 mm and 8.5 mm in both eyes, and the difference in pupil diameter between the right and left eyes is less than 0.4 mm. Pupil diameter will be measured in triplicate. The middle (median) value for each eye will be used to assess eligibility.
8. Screening ophthalmic exam performed by an ophthalmologist or similarly licensed professional (including assessment of visual acuity, visual fields, intra-ocular pressure, and fundoscopy) identifies no clinically significant abnormalities. Note: Routine refractive errors are not exclusionary, with the exception of myopia with refractive error greater than -3D
9. Meet the following requirements:
a. Is a male who agrees to all of the following:
• To use an appropriate method of contraception, including a condom, from the first dose of study drug until greater than or equal to 90 days after the last dose of study drug. A male participant who had a vasectomy procedure must follow the same restrictions as a non-vasectomized male. This requirement is waived for male participants with male partners.
• To not donate sperm from the first dose of study drug until greater than or equal to 90 days after the last dose of study drug.
OR
b. Is a pre-menopausal female (confirmed via screening follicle stimulating hormone [FSH] test) who is of reproductive potential or surgically sterile due to hysterectomy or bilateral salpingectomy and:
• agrees to not donate eggs from the first dose of study drug for greater than or equal to 30 days after the last dose of study drug AND
• agrees to remain abstinent from heterosexual activitya from Screening through greater than or equal to 30 days after the last dose of study drug OR
• agrees to use (or have their partner use) a birth control method that is highly effective and has low user dependency from Screening through greater than or equal to 30 days after the last dose of study drug. Acceptable methods of birth control are:
- Progestogen-only implant (e.g. etonogestrel implant)
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner
a Abstinence can be used as the sole method of contraception if it is in line with the subject’s preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ethics committees. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Has participated in another investigational study within the following time period: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer or based on local regulations) prior to the Screening Visit. The window will be derived from the date of the last study procedure and/or AE related to the study procedure in the previous study to the Screening Visit of the current study.
2. Is an employee of the Sponsor or study site or immediate family member (eg, spouse, parent, child, sibling) of the Sponsor or study site.
3. Has a history of multiple significant and/or any severe allergies (eg, food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food.
4. Has a known hypersensitivity or contraindication to any component of K-3505, its excipients or related compounds.
5. Has a positive alcohol or drug screen at Screening and admission.
6. Has a positive pregnancy test at Screening and Period 1 Day -1.
7. Is a lactating/nursing female.
8. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency antibody, at the Screening Visit. Note: Subjects with positive hepatitis B virus or hepatitis C virus serology may be enrolled if quantitative polymerase chain reaction for hepatitis B virus or hepatitis C virus ribonucleic acid is negative.
9. Has a fever at screening* or has a positive COVID-19 test or a fever at Period 1 Day -1.
10. Had major surgery or donated or lost 1 unit of blood or blood products (approximately 500 mL) within 4 weeks prior to Period 1 Day -1.
11. Is unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication and through the completion of study participation at the Follow-Up visit. Exceptions are noted below..
12. Has excessive consumption of alcohol within 6 months prior to screening (greater than 14 drinks/week for males and greater than 7 drinks/week for females, where l drink is equal to 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) or use of soft drugs (such as marijuana) within 3 months prior to Screening, or hard drugs (such as cocaine) within 6 months prior to Screening.
12. Is unwilling or unable to refrain from study alcohol restrictions:
- Subjects must not consume any alcohol from 3 days (at least 72 hours) prior to check-in through discharge from the unit in each period, and from 3 days (at least 72 hours) prior to the poststudy visit.
- At all other times, alcohol consumption is limited to not more than 14 drinks per week for males and not more than 7 drinks per week for females where l drink is equal to 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor.
13. Is unable or unwilling to refrain from consuming caffeinated products from 24 hours prior to check-in through discharge from the unit in each period, and 24 hours prior to the follow up visit.
14. Has a substance abuse disorder.
15. Had a previous major psychotic disorder.
16. Has a corrected QT interval to Fridericia's formula (QTcF) greater than 450 milliseconds (msec) for males and greater than 470 msec for females at screening or predose on Period 1 Day 1.
17. Has a mean value for triplicate semi-recumbent systolic blood pressure greater than 140 mmHg and/or diastolic blood pressure greater than 90 mmHg measured after at least 10 minutes at rest at the Screening Visit or on Period 1 Day -1. If subject’s BP is over the limits, then one triplicate repeat may be taken after at least another 10 minutes of rest.
18. Has a mean value for triplicate semi-recumbent heart rate less than 60 bpm measured after at least 10 minutes at rest at the Screening Visit or on Period 1 Day -1. If this criterion is met, then one triplicate repeat may be taken after at least another 10 minutes of rest.
19. Has an estimated glomerular filtration rate (eGFR by the Chronic Kidney Disease Epidemiology [CKD-EPI] equation) less than 70 mL/min/1.73m2 at the Screening Visit or Period 1 Day -1.
20. Has alanine aminotransferase or aspartate aminotransferase (ALT or AST) of greater than 1.0X upper limit of normal (ULN) or total bilirubin greater than 1.5X ULN upper limit of normal (ULN) (isolated bilirubin greater than 1.5X ULN is acceptable if bilirubin is fractionated and direct bilirubin is within the laboratory normal range) at the Screening Visit or Period 1 Day -1.
21. Thyroid stimulating hormone (TSH) at screening is outside (above or below) the laboratory reference range.
22. Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, neurologic disorder, neoplastic, or genitourinary abnormalities or diseases.
23. Family history of congenital hypogonadotropic hypogonadism in a first-degree relative unless a specific genetic cause has been confirmed which does not involve mutation of TAC3R (the NK3R gene).
24. Subject meets any of the following:
- Any history of, or signs/symptoms consistent with a clinically significant ocular disease/condition (including eye injury).
- Myopia with refractive error greater than -3D in either eye, or myopia previously treated with refractive surgery (e.g. LASIK). Note: Other routine refractive errors are not exclusionary.
- Any history of ocular surgery, including refractive surgery (e.g. LASIK).
- Current routine use of any topical ophthalmic agents (including artificial tears) and/or planned/potential use during study participation.
- Personal or family history of any genetic condition that may predispose to retinal detachment including Stickler Syndrome, Marfan Syndrome, Ehler-Danlos Syndrome, Wagner Syndrome, and Familial Exudative Vitreoretinopathy. Note: A family history of such a condition is not exclusionary if results of genetic testing are provided which confirm the participant does not have the condition.
25. Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
26. Has a pregnant partner.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sponsor-generated, password protected allocation schedule will be emailed to unblinded pharmacy staff. Subjects will be assigned to Panel A or Panel B, then randomized to a treatment sequence within the assigned panel. This will result in subjects being assigned to K-3505 or placebo in a 3:1 ratio in each treatment period.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization will occur, using a randomization table created by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
No formal sample size calculations were made, as no formal hypothesis testing is planned for this study.

The Safety Analysis Set will consist of all subjects who are enrolled and receive study drug. No formal statistical tests or inference will be performed for safety analyses. All summaries will be reported and performed by K-3505 dose level.

The PK Analysis Set will consist of all subjects who receive study drug and have at least 1 measurable plasma concentration. PK parameters will be summarized using descriptive statistics.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/09/2024
Actual
Date of last participant enrolment
Anticipated
28/02/2025
Actual
Date of last data collection
Anticipated
13/03/2025
Actual
Sample size
Target
28
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 26740 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 42788 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 316783 0
Commercial sector/Industry
Name [1] 316783 0
KALLYOPE, Inc.
Country [1] 316783 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
KALLYOPE, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 319002 0
Commercial sector/Industry
Name [1] 319002 0
Avance Clinical Pty Ltd
Address [1] 319002 0
Country [1] 319002 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315551 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 315551 0
Ethics committee country [1] 315551 0
Australia
Date submitted for ethics approval [1] 315551 0
03/07/2024
Approval date [1] 315551 0
29/07/2024
Ethics approval number [1] 315551 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135058 0
Dr Richard Friend
Address 135058 0
Q-Pharm Pty Ltd, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 135058 0
Australia
Phone 135058 0
+61 7 3845 3620
Fax 135058 0
Email 135058 0
[email protected]
Contact person for public queries
Name 135059 0
Gabrielle Robb
Address 135059 0
Q-Pharm Pty Ltd, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 135059 0
Australia
Phone 135059 0
+61 7 3707 2784
Fax 135059 0
Email 135059 0
[email protected]
Contact person for scientific queries
Name 135060 0
Dr Richard Friend
Address 135060 0
Q-Pharm Pty Ltd, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 135060 0
Australia
Phone 135060 0
+61 737072720
Fax 135060 0
Email 135060 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No other documents available


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.